Peocolipase and enterostatin- Functions during high-fat feeding

Enterostatin is a peptide formed in the stomach and intestine during the activation of pancreatic/gastric procolipase. Procolipase is a necessary cofactor for lipase. These two proteins contribute to the breakdown of dietary triglycerides in the intestine. Enterostatin has been found to act as a satiety factor, selectively inhibiting fat intake both through sites in the gastrointestinal tract and through sites in the central nervous system, including the hypothalamus and amygdala. In this thesis the amino acid sequence of enterostatin from rat, mouse cat and pig was determined. Rat and mouse had the sequence APGPR, while cat and pig had the sequence VPDPR. The amount of colipase in relation to lipase was also investigated and found to be 0.5 for rat and mouse and 3 in cat and pig. Enterostatin (APGPR), supplied in the food for 25 days, was found to decrease body weight and high-fat food intake in mice housed at 29°C. At the same time enterostatin increased the mRNA expression of uncoupling protein 1 (UCP1) in brown adipose tissue and the expression of UCP2 in stomach and duodenum. The tissue uptake of procolipase was examined in rat. Procolipase was taken up through active transport mechanisms by the upper gastrointestinal tract (stomach, duodenum, ileum and pancreas) as well as by the brain. The long-tem effect of high-fat feeding on the mRNA expression of pancreatic lipase and colipase was investigated. High-fat feeding decreased the mRNA expression of both lipase and colipase at the end of the experimental period. These studies show that enterostatin is involved in the long-term regulation of body weight, probably by decreasing high-fat food intake and increasing thermogenesis. Also, an alternative way for enterostatin to reach the brain was identified via the uptake of procolipase.